Xeroderma pigmentosum (XP) is a hereditary disease in humans. It is characterized by extreme sensitivity to sunlight and to sun-induced skin disorders such as actinic damage and cancer. Cultured cells from XP patients have defective DNA repair mechanisms and are more sensitive to UV-light than are cells obtained from healthy individuals. The specific DNA repair defect in XP cells has not been characterized, but ample evidence suggests that it may be in the incision step of the nucleotide excision-repair pathway. The objectives of this research are to: (1) examine the abilities of sonicated, cell-free extracts from different XP complementation groups and from XP variant cells to excise thymine dimers from their endogenous chromatin, (2) perform in vitro complementation experiments with XP complementation groups that are shown to be defective in excision repair, and (3) investigate the dimer-excising ability of normal and XP cell-free extracts prepared by methods other than sonication.